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Stereotactic Body Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Stage IIA-B Prostate Cancer

NCT03367702

Description:

This randomized phase III trial studies how well stereotactic body radiation therapy works compared to intensity-modulated radiation therapy in treating patients with stage IIA-B prostate cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Stereotactic body radiation therapy may work better in treating patients with prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Stereotactic Body Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Stage IIA-B Prostate Cancer
  • Official Title: Phase III IGRT and SBRT vs IGRT and Hypofractionated IMRT for Localized Intermediate Risk Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: NRG-GU005
  • SECONDARY ID: NCI-2017-01398
  • SECONDARY ID: NRG-GU005
  • SECONDARY ID: NRG-GU005
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03367702

Conditions

  • Stage II Prostate Adenocarcinoma

Purpose

This randomized phase III trial studies how well stereotactic body radiation therapy works compared to intensity-modulated radiation therapy in treating patients with stage IIA-B prostate cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Stereotactic body radiation therapy may work better in treating patients with prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine whether stereotactic body radiation therapy (SBRT) can be shown to be
      superior to hypofractionated intensity-modulated radiation therapy (IMRT) in terms of
      genitourinary (GU) and gastrointestinal (GI) toxicity by having fewer patients that
      experience a minimal important decline (MID) in urinary irritation/obstructive and bowel
      Health Related Quality of Life (HRQOL) as measured by Expanded Prostate Cancer Index
      Composite (EPIC)-26 at 24 months post completion of therapy.

      SECONDARY OBJECTIVES:

      I. To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28
      fractions of 2.5 Gy) as measured by disease free survival (DFS).

      II. To determine whether SBRT can be shown to be superior to hypofractionated IMRT at 12 and
      24 months post completion of therapy in terms of HRQOL by having fewer patients that
      experience a minimal important decline (MID) bowel (12 months only) sexual, hormonal, urinary
      irritation/obstructive (12 months only) and in urinary incontinence HRQOL as measured by
      EPIC-26.

      III. To determine if SBRT (5 fractions of 7.25 Gy) is superior to hypofractionated IMRT (28
      fractions of 2.5 Gy) as measured by biochemical failure, overall survival, local failure,
      prostate cancer specific survival, and distant metastases.

      IV. To determine if prostate imaging-reporting and data system (PIRADS)version (v)2 = 4/5
      disease is predictive for biochemical failure.

      TERTIARY OBJECTIVES:

      I. To determine whether a potentially more expensive therapy, SBRT, would be cost-effective
      than standard hypofractionated IMRT as measured by the European Quality of Life Five
      Dimension Five Level Scale Questionnaire (EQ-5D-5L).

      II. To determine if disease characteristics captured on MRI can be used to predict which
      patients will respond to SBRT versus hypofractionated IMRT.

      III. Collect specimens for future translational research analyses.

      OUTLINE: Patients are randomized into 1 of 2 arms.

      ARM I: Patients undergo IMRT once daily for 5 fractions per week for 28 fractions over less
      than 32 business days.

      ARM II: Patients undergo SBRT at least every other day for 2-3 fractions per week for 5
      fractions over less than 12 business days.

      After completion of study treatment, patients are followed up every 6-12 months until death
      or study termination.
    

Trial Arms

NameTypeDescriptionInterventions
Intensity-Modulated Radiation Therapy (IMRT)Active ComparatorPatients undergo Intensity-Modulated Radiation Therapy (IMRT) once daily 5 fractions per week for 28 fractions over less than 32 business days.
    Stereotactic Body Radiation Therapy (SBRT)ExperimentalPatients undergo Stereotactic Body Radiation Therapy (SBRT) at least every other day for 2-3 fractions per week for 5 fractions over less than 12 business days.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Previously untreated (no local therapy such as surgery, radiation cryotherapy, HIFU,
                   etc.) localized adenocarcinoma of the prostate with the following clinical findings:
      
                     -  Clinical stage by digital rectal exam of either T1c or T2a/b (limited to one side
                        of the gland); (American Joint Committee on Cancer [AJCC], version 7) or cT1a-c
                        or 2a or 2b,
      
                     -  Stages T1a-T1b are eligible if patient underwent transurethral prostatic
                        resection (TURP), the patient must meet one of the following 3 criteria: 1)
                        Gleason score must be Gleason 7(3+4) with a PSA < 20 ng/mL, or 2) Gleason 6(3+3)
                        with a PSA > 10 ng/mL and < 20 ng/mL; (AJCC, version 7) or 3) Group Grade 1 or 2
      
                          -  If patient is receiving a 5-alpha reductase inhibitor at the time of
                             enrollment the baseline PSA value may be double the initial value and the
                             medication should be discontinued but a washout period is not required to
                             eligible, a PSA drawn while still on the medicine must be:
      
                               -  < 10 ng/mL if Gleason 7(3+4) (Note: This patient would be on
                                  stratification level 1 if PSA < 5 ng/mL and stratification level 2 if
                                  less than 10 ng/mL).
      
                               -  > 5 ng/mL and less than 10 ng/mL for Gleason 6(3+3) (Note: This
                                  patients would be on stratification level 3).
      
                     -  Percent of submitted positive core biopsies must be < 50% of all sextants
                        (Sextant refers to the bilateral base, mid and apex of the gland and the left and
                        right, resulting in six sections or sextants. Biopsies may take 2 from each
                        sextant. If more than 12 are sampled, some may be from a targeted region possibly
                        with multiple cores to ensure adequate tissue.)
      
                          -  NOTE: all cores from a targeted lesion will be counted as an N of 1 core for
                             calculating percent positive cores in total
      
                     -  The prostate volume must be < 60 cc as reported at time of biopsy or by separate
                        measure with ultrasound or other imaging modalities including magnetic resonance
                        imaging (MRI) or computed tomography (CT) scan
      
                     -  Patients in active surveillance who elect to be treated are eligible if they meet
                        protocol requirements
      
                -  History and physical including a digital rectal exam 60 days prior to registration
      
                -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 60 days prior to
                   registration
      
                -  MRI of pelvis (compliant with PIRADSv2 guidelines) within 90 days prior to
                   registration
      
                -  Bone scan or sodium fluoride positron emission tomography (PET) scan within 90 days
                   prior to registration
      
                -  Charlson modified co-morbidity score =< 3 for patients under 60 and =< 4 for patients
                   60 and over 21 days prior to registration
      
                -  International prostate symptom score (IPSS) of < 15 21 days prior to registration
      
                -  The patient must provide study-specific informed consent prior to study entry
      
                -  Willingness and ability to complete the Expanded Prostate Cancer Index Composite
                   (EPIC-26) questionnaire
      
                -  Completion of all items of the EPIC-26 which will be data entered at registration 60
                   days prior to registration
      
                -  Only English, Spanish, and French-speaking patients are eligible to participate
      
              Exclusion Criteria:
      
                -  Definitive clinical or radiologic evidence of metastatic disease; no nodal involvement
                   or evidence of metastatic disease allowed as defined by screening of the pelvis and a
                   bone scan or sodium fluoride PET scan
      
                -  Definitive T3 disease on MRI
      
                -  Prior or current invasive malignancy with current evidence of active disease within
                   the past 3 years
      
                -  Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
                   different cancer is allowable; must be off treatment for at least 3 years; [applicable
                   only to studies that incorporate systemic therapy]
      
                -  Prior radiotherapy to the region of the study cancer that would result in overlap of
                   radiation therapy fields
      
                -  The use of hormonal therapy is not allowed; if the patient in on a 5-alpha reductase
                   inhibitor, then they should be stopped prior to treatment once enrolled onto the
                   study; no washout period is required for this study to participate
      
                -  Severe, active co-morbidity defined as follows:
      
                     -  Human immunodeficiency virus (HIV) positive with CD4 count < 200
                        cells/microliter; Note that patients who are HIV positive are eligible, provided
                        they are under treatment with highly active antiretroviral therapy (HAART) and
                        have a CD4 count >= 200 cells/microliter within 30 days prior to registration;
                        Note also that HIV testing is not required for eligibility for this protocol
      
                     -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                        note, however, that laboratory tests for liver function and coagulation
                        parameters are not required for entry into this protocol; (patients on Coumadin
                        or other blood thinning agents are eligible for this study)
      
                -  Contraindication to MRI
      
                     -  Cardiac pacemaker or defibrillator
      
                     -  Surgically implanted electrical devices such as spinal stimulation devices or
                        intracranial stimulation devices, cochlear implants, the presence of metallic
                        foreign bodies in the orbits, and incompatible old mechanical heart valves and
                        aneurysm clips
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Male
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Incidence of Patients-Reported Gastrointestinal and Genitourinary Toxicity
      Time Frame:Up to 2 years
      Safety Issue:
      Description:Will be measured by Expanded Prostate Cancer Index Composite-(EPIC) 26 bowel and urinary irritation domains. Will be compared between treatment arms using a test of proportions with two-sided significance level of 0.05.

      Secondary Outcome Measures

      Measure:Biochemical Failure
      Time Frame:yearsFrom the date of randomization to the date of biochemical failure, date of precluding death, or last known follow-up, assessed up to 5 years.
      Safety Issue:
      Description:Will be assessed by Phoenix definition.
      Measure:Distant Metastasis
      Time Frame:From the time of randomization to the date of distant metastasis, date of precluding death, or last known follow-up date , assessed for up to 5 years
      Safety Issue:
      Description:Will be assessed.
      Measure:Health Related Quality of Life
      Time Frame:Up to 2 years
      Safety Issue:
      Description:Will be measured by EPIC-26 urinary incontinence, sexual, and hormonal domains.
      Measure:Incidence of adverse events (AEs)
      Time Frame:Up to 2 years
      Safety Issue:
      Description:Will be assessed by Common Terminology Criteria for Adverse Events version 4. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The number of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms. A comparison between treatment arms of grade 3 and higher genitourinary (GU) and gastrointestinal (GI) events related to treatment (separately) will also be tested. There are 5 pre-specified AEs, dysuria, hematuria, incontinence, rectal bleeding,
      Measure:Local Failure
      Time Frame:From the time of randomization to the date of local failure, date of precluding death, or last known follow-up date, assessed for up to 5 years
      Safety Issue:
      Description:Will be assessed.
      Measure:Overall Survival
      Time Frame:From the date of randomization to the date of death or last known follow-up date, assessed up to 5 years
      Safety Issue:
      Description:Will be estimated using the Kaplan-Meier method and treatment arms compared using the stratified log-rank test.
      Measure:Presence of Prostate Imaging-Reporting and Data System version (PIRADSv) 2 = 4/5 disease
      Time Frame:Baseline
      Safety Issue:
      Description:Will be assessed by magnetic resonance imaging (MRI).
      Measure:Prostate Cancer Specific Survival
      Time Frame:yearsFrom the date of randomization to the date of prostate cancer death, date of precluding death, or last known follow-up date, assessed up to 5 years
      Safety Issue:
      Description:Will be assessed.
      Measure:Regional Failure
      Time Frame:From the time of randomization to the date of local failure, date of precluding death, or last known follow-up date, assessed for up to 5 years
      Safety Issue:
      Description:Will be assessed.

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:NRG Oncology

      Last Updated

      September 3, 2019